Ticino, Italy

Functional Capacity in Anderson-Fabry Disease Patients

Microplastics and Nanoplastics (MNPs) in Patients With ST-elevation Myocardial Infarction (STEMI)

The FOCUS-ADHF Registry

This is a real-life, observational, prospective multicenter registry. Patients fulfilling inclusion and exclusion criteria will be consecutively enrolled in enrolling center. Enrolled patients will be treated at each treating physician's discretion referring to the general recommendation of the last ESC guidelines on management of acute heart failure as well as local practice. General guidelines for vasodilators use will be shared among enrolling centers to increase uniformity of treatment in case of prescription of this strategy. -After achievement of adequate decongestion, iv vasodilators infusion (if used) will be weaned and HF medications introduction/titration up to guidelines recommended doses. Other therapeutic interventions: will be left to treating physician discretion aiming to decongest the patient. Starting inotropes, vasopressors, mechanical cardiac support device (MCS) and use of non-invasive and/or invasive ventilation as well as continuous renal replacement therapies (CRRT) will be left to the treating physicians' discretion according to clinical course.

Cell Free DNA Profiling As a Tool to Monitor Clinically-Relevant Events in Allogeneic Hematopoietic Stem Cell Transplantation

PK/PD Analysis of Ceftazidime/Avibactam or Cefiderocol With or Without Fosfomycin for the Treatment of Difficult To-treat Gram-negative Infections

Gram-negative infections, particularly those caused by Carbapenem-resistant Enterobacterales (CRE), have a dramatic impact on patient survival. Despite the introduction of new drugs in the last years have improved the outcome of patients with difficult-to-treat gram-negative infections, mortality and relapse rates are still relevant, especially in patients with high-risk sources such as pneumonia, and those in which the attainment of optimal exposure could be reduced by underlying renal disease. The use of a combination regimen in these scenarios has been proposed. However, a standardized approach to therapeutic management is still missing. To overcome this unmet clinical need, this study aims to investigate the pharmacokinetic/pharmacodynamics (PK/PD) optimization of antibiotic dosing regimens in patients with difficult-to-treat Gram-negative infections, using Therapeutic Drug Monitoring (TDM). A prompt implementation of an appropriate targeted antibiotic therapy could represent a valuable approach to improve clinical outcomes in patients with difficult-to-treat Gram-negative infections. Moreover, more information is needed in pediatric populations where ceftazidime/avibactam (CAZ/AVI) is approved only for children aged > 3 months (with the same indications as adults) and cefiderocol (CEF) is not approved. Indeed, cefiderocol is currently off-label administered in pediatric population using case-by-case dosages based on encouraging case reports. Since several in vitro studies have highlighted the synergistic effect of fosfomycin (FOS) with different antibiotic classes, including cephalosporins such drug could be an appealing option in combination therapy for the management of difficult-to-treat gram-negative infections, both with CAZ/AVI and CEF. However, real-life prospective studies are needed to investigate the potential benefit of combination therapy on clinical outcomes and the occurrence of further resistance. Thus, the correct dose of FOS along with the type of administration (i.e., intermittent, extended, or continuous infusion) are issues to establish. In particular, the primary aim of the study is to evaluate the probability of achieving pre-determined pharmacokinetic/pharmacodynamic (PK/PD) efficacy targets for CAZ/AVI, CEF and FOS. Secondary objectives are: - to evaluate the relationship between the achievement of the PK/PD target of CAZ/AVI, CEF and FOS and microbiological eradication; - to evaluate the trend of clinical biomarkers in response to antibiotic therapy; - to investigate the diagnostic and prognostic value of protein biomarkers. This research is supported by EU funding within the Next Generation EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT).

Characterisation of the Biochemical Profile and Physiology of the Coronary Circulation in Takotsubo Syndrome

Intracoronary Optical Coherence Tomography Guidance Vs. Angiography Only Guidance for Treatment of Coronary In-stent Restenosis

INSIDE-OCT is an investigator-initiated, randomised, multicenter, non-blinded trial. Patients presenting with acute coronary syndrome or stable ischemic heart disease and ISR (angiographic stenosis between 70% and 99% in at least two projections, in a vessel with a lumen diameter ≥ 2.25 - ≤ 5.75 mm) with PCI indication will be randomised (1:1) to undergo either PCI guided by OCT (Group 1) or PCI with angiographic guidance only (Group 2). Nowadays, PCI is performed following current guidelines and clinical practice. Any manoeuvre is left to the operator's discretion. Any approved intracoronary gears could be used (multiple wires, compliant, non-compliant, cutting, scoring balloons, Drug coated balloons, new stents implantation etc.). Randomisation will be performed on the online eCRF site immediately after the end of the diagnostic angiography after acquiring the patient's study informed consent and after reviewing inclusion/exclusion criteria. Randomisation will generate two groups: PCI of ISR guided by OCT (group 1): in this case, the operator has to perform at least one OCT run before and one OCT run at the end of PCI. The operator is left free to review the OCT run in the console directly and is left free to perform during PCI any additional OCT run. PCI of ISR guided by angiography (group 2): in this case, the operator has to perform PCI following angiography. To allow outcome computation, OCT will also be performed in this group at the beginning and the end of PCI. However, the operator will be wholly blinded to any OCT findings. A detailed description of the blinding modality is reported in the following paragraph. Blinding: In Group 2, OCT will be performed at the beginning of the procedure, although the operator will be blinded to any OCT findings. In practice, the operator will perform OCT pullback properly, advancing the probe in the target vessel following angio guidance but without viewing the OCT monitor in the cath lab. A trained nurse/technician not involved in any decision regarding the procedure will guide the operator to perform an OCT pullback correctly and will check immediately if the OCT run is consistent with the current standard of quality. The operator could not receive any information from the OCT run recorded at this stage and had to proceed with the PCI procedure with angio-only guidance Therefore, the operator will declare the end of the procedure after completing all PCI manoeuvres judged necessary to obtain an excellent angiographic result. At this stage, an OCT pullback will be performed again to appraise OCT final data required for primary endpoint computation. Therefore, the operator should evaluate the OCT runs, and he will be left free to perform additional PCI manoeuvres to optimise the result if necessary. In groups 1 and 2, the operator should detail his PCI planned strategy before and after OCT runs. Changes in PCI planning after OCT disclosure will be recorded in both groups (see secondary outcomes).

Erdafitinib Monotherapy or in Combination With Cetrelimab in Muscle-invasive Bladder Cancer Patients With Fibroblast Growth Factor Receptor (FGFR ) Gene Alterations

The aim of the study is to assess the antitumor activity measured as ypT0 rate, defined as no evidence of residual disease based on pathological review of the surgical specimen (pCR) and tumour downstaging (<ypT2). Patients must have a MIBC (cT2-T4a N0/N1 M0) who harbour selected FGFR alterations stated in the protocol and are either ineligible for or refuse cisplatin-based neoadjuvant chemotherapy, as defined by consensus criteria (see 6.1 Inclusion criteria). Once it is confirmed that the subjects fulfil the eligibility criteria and have signed the informed consent form, they will receive erdafitinib alone (cohort 1) or erdafitinib in combination with cetrelimab (cohort 2). Patients will receive neoadjuvant treatment with erdafitinib alone (cohort 1) or erdafitinib plus cetrelimab (cohort 2) before proceeding to Radical Cystectomy (RC) (to be performed within 2 - 6 weeks after the last study drug treatment) Cohort 1: patients will receive erdafitinib Cohort 2: patients will receive erdafitinib in combination with cetrelimab intravenously (IV) Radiological assessment: A Computed Tomography /Magnetic Resonance Imaging and/or Positron Emission Tomography (per standard local imaging practices) will be scheduled as follow: - Basal assessment: during screening period (no more than 28 days before Cycle1, Day 1(C1D1) - Response assessment: At the end of treatment period allowing time for imaging review in advance of Radical cystectomy (RC). - Follow-up assessment: an image evaluation must be done at first follow-up visit and thereafter, it will be schedule according to local standards and as clinically indicated. A local pathological assessment will be done on specimens obtained during RC (for co-primary endpoints). Thereafter, during the follow-up period, pathological assessments will be scheduled according to local standards and as clinically indicated. Patients with disease progression during the treatment phase will be discontinued from the study and will receive their treatment according to the investigator's judgment and monitored to evaluate Overal Survival .

Trial of Efficacy and Safety of MC0518 Versus Best Available Therapy in Participants with Steroid-Refractory Acute Graft Versus Host Disease

Safety and Efficacy of RVU120 Combined With Venetoclax for Treatment of Relapsed/Refractory AML

In Part 1 dose-escalation participants will receive escalating oral doses of RVU120 starting at 125 mg administered every other day on days 1-13, and escalating oral doses of venetoclax starting with 200 mg administered daily on days 1-14 of each 21-day cycle of treatment. The recommended doses for further study will be based on the observed safety, tolerance, PK and PD. In Part 2, it will be assessed whether the recommended dose level from Part 1 reaches the targetted response criteria, and if reached, Part 3 will be initiated to further evaluate the efficacy and safety of the recommended doses in a larger population.